This invention relates to measuring connective tissue breakdown products and muscle tissue breakdown products in a body fluid from an animal.
A breakdown of crosslinked fibrous elastin and crosslinked fibrous collagen, hereafter referred to as elastin and collagen or connective tissue components, is believed to be involved in the pathogenesis of some chronic diseases. In chronic obstructive pulmonary disease and in cystic fibrosis, for instance, the elastase and neutrophil load in the lungs is increased, and elastin and collagen destruction in the lungs is believed to be an ongoing part of the disease process. Also, the proteolytic digestion of lung elastin is thought to be a primary event of the alveolar wall destruction that occurs in the pathogenesis of pulmonary emphysema.
Desmosine and isodesmosine are cross-linking amino acids present in elastin. Because desmosine and isodesmosine are unique to elastin, they are recognized as established specific markers for crosslinked fibrous elastin and elastin degradation products in mammalian tissues and fluids. Moreover, desmosine and isodesmosine are not metabolized, and are passed directly to the urine, and for these reasons, some attempts to monitor elastin breakdown products as an indication of the condition of the alveolar walls have been directed to measuring urinary desmosine.
Measurements of urinary desmosine by means of radioimmunoassay have to date failed to support an elastase-antielastase hypothesis of emphysema, suggesting to some workers that the monitoring of elastin degradation products does not provide an indication of disease processes that effect elastin breakdown.
Pyridinoline and deoxypyridinoline are cross-linking amino acids present in collagen. Pyridinoline and deoxypyridinoline are used as specific markers for collagen and for collagen degradation products because they are unique to collagen, and they are not metabolized but are passed directly to the urine.
A breakdown of muscle tissue is believed to be involved in some pathologic conditions, and a decrease in the quantity of muscle breakdown components is believed to be a component of protein-calorie malnutrition. Catabolism of muscle protein results in the excretion of 3-methylhistidine, also known as N-methylhistidine in the urine. Measurement of 3-methylhistidine in the urine can provide an assessment of muscle protein breakdown, since the major source of 3-methylhistidine in the body fluids is from the muscle proteins, actin and myosin.